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Although bariatric surgery is associated with multiple health benefits, decreased bone mass is a known complication of the procedure. Roux-en-Y gastric bypass (RYGB) is associated with significant bone loss and increased fracture risk. However, data on the effect of sleeve gastrectomy (SG) on bone mineral changes are sparse. The impact of vitamin D and calcium levels on bone mineral density (BMD) after SG is also unknown. A retrospective chart review was performed to include patients who underwent RYGB or SG from 2014 to 2016 at a single institution. Patients were included if bone densitometry was performed preoperatively and within 2 years postoperatively. Serum 25-hydroxy vitamin D and calcium levels were collected preoperatively and at time of bone densitometry scan. BMD and T-score changes at the femoral neck, femoral trochanter, total hip, and lumbar spine were compared between RYGB and SG patients. A total of 40 patients were included. 24 (60%) of patients underwent RYGB and 16 (40%) patients underwent SG. No statistically significant difference in baseline characteristics was noted between RYGB and SG patients. All measurements, except for serum 25-hydroxy vitamin D, were significantly decreased in RYGB patients, postoperatively. All measurements, except for BMD and T-score at the lumbar spine and serum 25-hydroxy vitamin D, were significantly decreased in SG patients, postoperatively. The extent of decrease in serum 25-hydroxyvitamin D was significantly associated with decreased BMD (p = 0.049) and T-score (p = 0.032) at the lumbar spine. The extent of decrease in serum calcium was significantly associated with decreased BMD (p = 0.046) at the femoral neck. All patients were found to have decreased BMD after RYGB and SG. Surgery type was not a significant risk factor in BMD change. Despite vitamin D and calcium supplementation in all patients, a decrease in vitamin D and calcium levels were associated with a decrease in BMD. Close follow-up and treatment of vitamin D and calcium levels are warranted in all bariatric patients.

Obesity is a known risk factor for many cancers. Although bariatric surgery has been associated with a decrease in the risk of developing cancer, data on the effect of bariatric surgery on female-specific cancers are limited. This study aimed to assess the impact of bariatric interventions on the development of endometrial, ovarian and breast cancer. The New York Statewide Planning and Research Cooperative System database was used to identify all female patients without a pre-existing cancer diagnosis who had a diagnosis of obesity between 2006 and 2012. The risk of having female-specific cancer diagnosis in patients who underwent bariatric surgery were compared with those who had no bariatric interventions using multivariable proportional sub-distribution hazard regression analysis. Subsequent cancer diagnoses were followed up to 2016. We identified 55,781 and 247,102 obese female patients who had and did not have bariatric surgery, respectively. The overall incidence of female-specific cancer was 2.69% and 2.09% for the non-surgery and surgery groups, respectively (p

Introduction: Angiotensin converting enzyme (ACE) 2, is a co-receptor for the entry of SARS-CoV-2 into target cells. The impact of ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on outcomes in patients with coronavirus disease 19 (COVID-19) is under investigation. Hypothesis: ACEIs/ARBs are associated with worse outcomes in patients hospitalized with COVID-19. Methods: We evaluated the in-hospital course of 469 adults admitted to Stony Brook University Hospital, NY, from March 1 to April 15, 2020 with severe COVID-19 pneumonia (need for high-flow O2). We excluded patients who required mechanical ventilation (MV) or died within 24h of admission. We used Cox regression models to examine the association of previous (home) use of ACEIs or ARBs with mortality and the composite of death or MV. Results: Table 1 summarizes the patient characteristics according to ACEI/ARB use (ACEI: 73; ARB: 73; 146/469 patients, 31.1%). After a median of 13 days (8-22), 123 patients (26.2%) died and 105 patients (22.4%) required MV and survived. In models adjusting for age, sex, race, body mass index, hypertension, diabetes, coronary artery disease, heart failure, atrial fibrillation, chronic lung disease, chronic kidney disease, and baseline 0 2 saturation, ACEIs/ARBs were not associated with mortality (HR 1.00; 95%CI 0.62-1.61; P=0.99). There was no difference between classes in mortality (ACEI vs. ARB: HR 1.14; 95%CI 0.61-2.15; P=0.68). However, there was a trend towards lower rates of death or MV with ACEI/ARB (HR 0.75; 95%CI 0.54-1.05; P=0.095), mainly because of lower MV rates. The protective effect of ARBs on the composite was significant (HR 0.66; 95%CI 0.44-0.99; P=0.046) whereas that of ACEIs was not (HR 0.87; 95%CI 0.57-1.31; P=0.50), albeit difference was not significant (P=0.28). Conclusions: In patients with severe COVID-19 pneumonia, ACEI/ARB use was not associated with mortality. Especially ARBs may reduce need for MV in this high-risk COVID-19 population.

Introduction: The value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in hospitalized patients with severe coronavirus disease 2019 (COVID-19) is unclear. Hypothesis: Elevated NT-proBNP is associated with worse prognosis in hospitalized COVID-19 patients regardless of history of HF. Methods: We evaluated the in-hospital course of 469 adults admitted to Stony Brook University Hospital, NY, from March 1 to April 15, 2020 with severe COVID-19 pneumonia (need for high-flow O 2 ). We excluded patients who required mechanical ventilation (MV) or died within 24h of admission. We used Cox regression models to examine the association of admission NT-proBNP with mortality and the composite of death or MV. Results: Admission NT-proBNP was available in 399 patients (85.1%) of this cohort. Table 1 summarizes the patient characteristics according to history of HF (41/399 [10.3%]). After a median of 13 days (8-22), 107 patients (26.8%) died and 86 additional patients (21.6%) required MV and survived. Both HF (HR 3.65; 95%CI 2.32-5.77; P2 saturation, every log-2 higher admission NT-proBNP was associated with 28% higher mortality in patients with HF (HR 1.28; 95%CI 1.02-1.61; P=0.037) and 26% higher mortality in patients without HF (HR 1.26; 95%CI 1.14-1.40; P Conclusions: In these high-risk COVID-19 patients, admission NT-proBNP was strongly predictive of mortality regardless of HF. Elevated NT-proBNP may thus identify patients in need of cardioprotective measures.

Background Heart failure is a disease with significant healthcare utilization and a prioritized target for readmission prevention. Although obesity is related to heart failure morbidity, the effects of bariatric surgery in obese patients with heart failure are not well studied. Objectives To evaluate the impact of bariatric surgery on hospital-based healthcare utilization for patients with heart failure. Setting Administrative statewide database. Methods The New York Statewide Planning and Research Cooperative System database was used to identify patients with obesity and heart failure who underwent bariatric surgery from 2005 to 2015. Emergency department (ED) visits and hospitalization records from 1 year presurgery and up to 2 years postsurgery were compared. Results Our study identified 899 patients with heart failure who underwent bariatric surgery. In the year presurgery, 11.48% of patients had any ED visit or hospitalization with a primary diagnosis of heart failure. The rate decreased drastically in the first year after surgery, with only 3.70% of patients having any heart failure–related hospital visits. The rate of heart failure–related visits was also lower in the second year postsurgery (3.44%) compared with the year before surgery. The risk of heart failure–related hospital visits was lower in both the first year (odds ratio [OR], .29; 95% confidence interval [CI], .19–.43) and second year postsurgery (OR, .26; 95% CI, .17–.41; P Conclusions These findings suggest that bariatric interventions might be associated with decreased risks of ED visits or hospitalizations due to heart failure exacerbations in obese patients with preexisting heart failure.

Background Sociodemographic disparities in terms of access to bariatric surgery are ongoing. Objectives This study aimed to examine the trends for bariatric interventions based on patient characteristics from 2011 to 2018 in the state of New York. Setting Administrative statewide database. Methods This study used the New York Statewide Planning and Research Cooperative System database to identify all patients with obesity who underwent Roux-en-Y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (SG), and laparoscopic adjustable gastric banding (LAGB) between 2011 and 2018. The trends were studied for the types of bariatric procedures performed across different patient characteristics, including median household income as determined based on ZIP code. A multivariable logistic regression analysis was performed to compare the yearly trends. Results We identified 111,793 patients who underwent bariatric surgery. The number of bariatric procedures increased from 9304 in 2011 to 16,946 in 2018. RYGB was the most performed bariatric operation in 2011, but was replaced by SG from 2013 to 2018. Patients living in the highest decile median household income ZIP code areas had the highest increase in SG (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.46–1.55; P Conclusions The use of bariatric surgery increased significantly from 2011 to 2018. However, the disproportionately and substantially increased use of SG and the decreased use of LAGB in patients living in wealthier areas suggest that disparity in the use of bariatric interventions still exists. Public health efforts should be made to equalize access to bariatric surgery.

Obesity is a known risk factor for many cancers. Although bariatric surgery has been associated with a decrease in the risk of developing cancer, data on the effect of bariatric surgery on female-specific cancers are limited. This study aimed to assess the impact of bariatric interventions on the development of endometrial, ovarian and breast cancer.The New York Statewide Planning and Research Cooperative System database was used to identify all female patients without a pre-existing cancer diagnosis who had a diagnosis of obesity between 2006 and 2012. The risk of having female-specific cancer diagnosis in patients who underwent bariatric surgery were compared with those who had no bariatric interventions using multivariable proportional sub-distribution hazard regression analysis. Subsequent cancer diagnoses were followed up to 2016.We identified 55,781 and 247,102 obese female patients who had and did not have bariatric surgery, respectively. The overall incidence of female-specific cancer was 2.69% and 2.09% for the non-surgery and surgery groups, respectively (p 0.0001). Surgery patients were less likely to develop female-specific cancers [hazard ratio (HR) 0.78; 95% CI 0.73-0.83; p 0.0001]. Patients undergoing Roux-en-Y gastric bypass had a lower risk of developing female-specific cancer than laparoscopic sleeve gastrectomy (HR 0.66; 95% CI 0.51-0.87; p = 0.0056) and laparoscopic adjustable gastric banding (HR 0.83; 95% CI 0.69-0.99; p = 0.0056) patients.Patients undergoing bariatric surgery have a lower incidence of endometrial, female breast and ovarian cancer than non-surgery obese patients. These data suggest that bariatric interventions may reduce the risk of female-specific cancers.

Although bariatric surgery has been associated with a reduction in risk of obesity-related cancer, data on the effect of bariatric interventions on other cancers are limited.This study aimed to examine the relationship between bariatric interventions and the incidence of various cancers after bariatric surgery.Administrative statewide database.The New York Statewide Planning and Research Cooperative System database was used to identify all adult patients diagnosed with obesity between 2006 and 2012 and patients who underwent bariatric procedures without preexisting cancer diagnosis and alcohol or tobacco use. Subsequent cancer diagnoses were captured up to 2016. Multivariable proportional subdistribution hazard regression analysis was performed to compare the risk of having cancer among obese patients with and without bariatric interventions.We identified 71,000 patients who underwent bariatric surgery and 323,197 patients without a bariatric intervention. Patients undergoing bariatric surgery were less likely to develop both obesity-related cancer (hazard ratio.91; 95% confidence interval, .85-.98; P = .013) and other cancers (hazard ratio .81; 95% confidence interval, .74-.89; P.0001). Patients undergoing Roux-en-Y gastric bypass had a lower risk of developing cancers that are considered nonobesity related (hazard ratio .59; 95% confidence interval, .42-.83; P = .0029) compared with laparoscopic sleeve gastrectomy.Bariatric surgery is associated with a decreased risk of obesity-related cancers. More significantly, we demonstrated the relationship between bariatric surgery and the reduction of the risk of some previously designated nonobesity-related cancers, as well. Reclassification of nonobesity-related cancers and expansion of bariatric indications for reducing the risk of cancer may be warranted.

Background Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) can be serious complications of coronavirus disease 19 (COVID-19). Co-infections may worsen outcomes and prolong hospitalization. This risk may be exacerbated by systemic corticosteroids (steroids) and other adjunctive therapies. Methods We reviewed the records of all adults admitted to Stony Brook University Hospital, NY, from 3/1 to 4/15, 2020 with severe COVID-19 pneumonia, requiring high-flow O2 (non-rebreather mask, Venturi mask with FiO2 >50%, or high-flow nasal cannula). We excluded patients who received mechanical ventilation (MV) or died within 24h. Patients were followed until death or hospital discharge. We reviewed positive sputum cultures (PSC) for pathogenic microorganisms and calculated the incidence of HAP and VAP (nosocomial pneumonia, [NP]), rates of MV and impact on mortality. Fungi isolated from sputum, were considered colonization unless associated with fungemia. We also examined the impact of adjunctive therapies with immunosuppressive potential (steroids and tocilizumab), on HAP or VAP. Results A total of 469 patients were included (Table 1). Of these, 199 (42.4%) required intensive care and 172 (36.7%) MV. Median length of stay was 13 days (8–22) and 105 (22.4%) had PSC. Of these, 59 were considered true pathogens (HAP: 11, VAP: 48), with predominance of S. aureus (MSSA) 38.9%, Enterobacteriaceae 33.8% and Pseudomonas species 18.6%. 39 isolates were considered colonization (Table 2); Patients with PSC < 48h (N=7) from admission, were not considered NP. The incidence of NP was 7.0 per 1000 patient-days (95%CI 5.5–8.5). Of 11 patients with HAP, 9 needed MV. NP was more frequent among patients receiving steroids (9.0 vs 5.7 per 1000 patient-days; P=0.023). Use of tocilizumab was not associated with NP (6.2 vs 8.4 per 1000 patient-days; P=0.11). Mortality was nonsignificantly higher in patients with (20/59, 33.9%) vs. without (103/410, 25.1%) NP (P=0.16). Intubation and length of stay were the strongest predictors of NP in multivariable models. Cohort Characteristics of Patients with Severe COVID -19 Pneumonia on High Flow Oxygen (N= 469) All Microbes Isolated from Sputum Cultures Conclusion Among high risk COVID-19 patients, NP is a common complication. MSSA and Enterobacteriaceae were the most frequent isolates. The risk increases with intubation, longer hospital stay and use of steroids but not tocilizumab. Disclosures All Authors: No reported disclosures

Background Coronavirus disease 19 (COVID-19) leading to acute respiratory distress syndrome is associated with need for intensive care (IC), mechanical ventilation (MV), and prolonged recovery. These patients are thus predisposed to blood stream infections which can worsen outcomes. This risk may be aggravated by adjunctive therapies. Methods We reviewed the medical records of all adults admitted to Stony Brook University Hospital, NY, from March 1 to April 15, 2020 with severe COVID-19 pneumonia (requiring high-flow O2). Patients who received MV or died within 24h were excluded. Patients were followed until death or hospital discharge. We reviewed positive blood cultures (PBC) for pathogenic microorganisms, and calculated the incidence of bacteremia, rates of infective endocarditis (IE), and impact on mortality. Microbes isolated only once and belonging to groups defined as commensal skin microbiota were labelled as contaminants. We also examined the impact of adjunctive therapies with immunosuppressive potential (steroids and tocilizumab), on bacteremia. Results A total of 469 patients with severe COVID-19 pneumonia were included (Table 1). Of these, 199 (42.4%) required IC and 172 (36.7%) MV. Median length of stay was 13 days (8–22) and 94 (20.0%) had PBC. Of these, 43 were considered true pathogens (bacteremia), with predominance of E. faecalis and S. epidermidis, and 51 were considered contaminants (Table 2). The incidence of bacteremia (43/469, 9.2%) was 5.1 per 1000 patient-days (95%CI 3.8–6.4). An echocardiogram was performed in 21 patients, 1 had an aortic valve vegetation (IE) by methicillin sensitive S. aureus. Bacteremia rates were nonsignificantly higher with steroids (5.9 vs 3.7 per 1000 patient-days; P=0.057). Use of tocilizumab was not associated with bacteremia (5.8 vs 4.8 per 1000 patient-days; P=0.28). Mortality was nonsignificantly higher in patients with (15/43, 34.9%) vs. without (108/426, 25.4%) bacteremia (P=0.20). Length of stay was the strongest predictor of bacteremia, with risk increasing by 7% (95%CI 6%-9%, P< 0.001) per additional day. Cohort Characteristics of Patients with Severe COVID-19 Pneumonia on High-Flow O2 (N= 469) All Microorganisms Isolated from Blood Cultures Conclusion The incidence of bacteremia was relatively low and IE was uncommon in this study of severe COVID-19 patients. Risk of bacteremia increased with longer hospital stay and with steroids use, but not with tocilizumab. Disclosures All Authors: No reported disclosures

Although bariatric center procedural volume has been associated with early perioperative safety, data on the effect of such volume and long-term outcomes after sleeve gastrectomy (SG) are limited. This study aims to examine the relationship between annual bariatric center SG volume and the incidence of revisions or conversions (RC) after SG. The New York Statewide Planning and Research Cooperative System database was used to identify all patients who underwent SG between 2006 and 2012. Subsequent RC events were captured up to 2016. Bariatric centers having annual SG volume less than 45, between 45 and 65, and greater than 65 were defined as low (LV), medium (MV), and high volume (HV), respectively. Multivariable Cox proportional hazard regression analysis was performed to compare the risk of having RC among centers with different yearly sleeve volumes. We identified 8389 patients who underwent SG. The overall estimated cumulative incidence of RC was 0.5% (95% CI 0.3–0.6%) at 1 year, 6.2% (95% CI 5.4–7.0%) at 5 years, and 15.3% (95% CI 12.6–18.0%) at 8 years after SG. The estimated cumulative incidence of RC for LV, MV, and HV at 8 years after SG was 16.7% (95% CI 11.1–22.3%), 15.5% (95% CI 11.2–19.8%), and 13.7% (95% CI 9.4–17.9%), respectively. HV centers have lower risk of RC compared to LV (hazard ratio 0.65; 95% CI 0.48–0.88) and MV (hazard ratio 0.75; 95% CI 0.57–0.98). LV and MV centers have comparable risk of RC (hazard ratio 1.15; 95% CI 0.87–1.51). Patients having the initial SG performed in LV were the least likely to have RC in the same institution (46.1% of LV, 13.2% of MV and 22.3% of HV; p

Bruton tyrosine kinase (BTK) is a critical effector molecule for B cell development and plays a major role in lymphoma genesis. Ibrutinib is the first-generation BTK inhibitor. Ibrutinib has off-target effects on EGFR, ITK, and Tec family kinases, which explains the untoward effects of ibrutinib. Resistance to ibrutinib was also reported. The C481S mutation in the BTK kinase domain was reported to be a major mechanism of resistance to ibrutinib. This review summarizes the clinical development of novel BTK inhibitors, ACP-196 (acalabrutinib), ONO/GS-4059, and BGB-3111.

T790M mutation is the most common mechanism for resistance to first- and second-generation tyrosine kinase inhibitors (TKI) for epidermal growth factor receptor (EGFR). Several third-generation EGFR mutant selective TKIs are being explored to conquer this resistance. AZD9291 (osimertinib, tagrisso) has been approved for treatment of the metastatic EGFR T790M mutation-positive non-small cell lung cancer. Resistance to AZD9291 has been described. C797S mutation was reported to be a major mechanism for resistance to T790M-targeting EGFR inhibitors. This review summarizes the latest development in identifying the C797S mutation and EAI045, the novel selective inhibitor overcoming the C797S mutant.